The major objective of this research is to elucidate the chemical and physical properties of ligand-bridged, bimetallic centers in proteins and related model compounds. Specific studies will focus on imidazolate-bridged complexes as found at the active site of bovine erythrocyte superoxide dismutase (BESOD) and related enzymes. Nuclear magnetic resonance, chemical modification, gel electrophoresis, and metal substitution techniques will be used to refine our knowledge of the active site structure and subunit interactions in BESOD, wheat germ SOD, and bacteriocuprein. These methods, together with electron spin resonance investigations of the reaction of the SOD enzymes with O minus over 2 in aprotic solvents, will be employed to probe the mechanism of action of the imidazolate-bridged copper-zinc center. In the parallel studies, imidazolate-bridged, binuclear metal complexes will be synthesized and charaterized as models for the active sites of BESOD and related Cu-Zn and Cu-Fe enzymes. Criteria will be developed to identify histidine (imidazolate)-bridged metal centers in protein. Molecular structures will be determined by x-ray crystallography. The effects of ligand structure and the choice of metal ion on the chemical reactivity, redox properties, and the physical characteristics of the imidazolate-bridged complexes will be investigated using spectral, electrochemical, and magnetic susceptibility apparatus. Special attention will be given to potential imidazolate-bridge-splitting processes in the reactions of both the enzyme and the model compounds with superoxide ion and related anionic inhibitors, reducing agents, and acid. Fundamental knowledge of these systems will complement recent biological work that has established the role of superoxide dismutase in defending against pulmonary oxygen toxicity, reducing paraquat toxicity, and protecting synovial fluid against O minus over 2 generated in phagocytosis.